AEG-1 3'-untranslated region functions as a ceRNA in inducing epithelial-mesenchymal transition of human non-small cell lung cancer by regulating miR-30a activity

Abstract

Competitive endogenous messenger RNA regulates the transcription of other RNA moleculars through competing for the shared microRNAs. This study was carried out to explore the regulation of AEG-1 messenger RNA as a competitive endogenous RNA in the epithelial-mesenchymal transition and metastasis of lung tumor cells. It is shown that the epithelial-mesenchymal transition was associated with the down-regulation of miR-30a, up-regulation of AEG-1 and mesenchymal markers (Snail and Vimentin); miR-30a inhibited the metastasis of lung tumor A549 cells in vitro, whereas AEG-1 promoted it. These results suggested the potential linkage between miR-30a and genes (AEG-1, Snail and Vimentin) in the epithelial-mesenchymal transition and metastasis of lung tumor cell. It was verified later that the 3'-untranslated regions of AEG-1, Snail and Vimentin bind to miR-30a in A549 cells. Therefore, a competitive endogenous RNAs regulatory network among AEG-1, Snail and Vimentin mediated via competitive binding to miR-30a was proved. That is, the 3'-untranslated region of AEG-1, functioning as the competitive endogenous RNAs, indirectly regulated the expression of Vimentin and Snail in inducing epithelial-mesenchymal transition of human non-small cell lung cancer. In conclusion, our findings demonstrated a competitive endogenous RNAs regulatory network which will help understand the metastasis mechanisms of lung cancer and improve the prevention and treatment of lung cancer.

Keywords: AEG-1; Competitive endogenous RNAs (ceRNAs); Epithelial–mesenchymal transition (EMT); Lung cancer; Snail; Vimentin; miR-30a.